This R21 application proposes a novel use of naltrexone as treatment for Pathological Gambling Disorder (PGD) patients with severe urge symptoms. Although PGD is a prominent and growing social problem, there is no established drug treatment for this disorder. Our preliminary investigations demonstrate statistically significant findings that an opioid antagonist, may serve as a viable treatment option for PGD patients with severe urges. In 1994, naltrexone was approved to treat alcoholism (at a dose limited to 50 mg/day, but the use of naltrexone has since languished. In an effort to further pursue the use of naltrexone, we adopted a novel alternative approach. First, we focused our efforts only on a subset of PGD patients who had severe urge symptoms, as opposed to the entire PGD population. Second, we tested naltrexone at doses higher than 50 mg/day (up to 250 mg/day). Third, we addressed the side effect of hepatic transaminase revelation, an established adverse effect of naltrexone at doses above 50 mg/day, and we found a solution, such that dosages up to 250 mg/day were well tolerated and safe during an 11-week time period of use. In our three preliminary investigations, we found statistically significant results in our case study, open study, and double blind study, showing that naltrexone doses above 50 mg/day are effective in treating PGD patients with severe urges. We present the design of our proposed double-blind study, placebo-controlled, dose-finding study, which will expand upon our preliminary work and will establish the optimal dose for efficacy, whether efficacy is maintained for 16 weeks, and whether efficacy is disrupted in a male: female ratio analogous to that of the PGD population in the U.S. The implications of our study expand from PGD to other impulse control disorders, including compulsive shopping, kleptomania and possible alcoholism.